The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Apr. 07, 1998
Filed:
Nov. 10, 1994
Vitukudi Narayanaiyengar Balaji, Encinitas, CA (US);
Ming Fai Chan, San Diego, CA (US);
Texas Biotechnology Corporation, Houston, TX (US);
Abstract
Cyclic peptides and pharmaceutically acceptable salts and esters thereof are provided. The cyclic peptides and pharmaceutically acceptable salts and esters thereof mimic surface features of the C-terminus of endothelin and thereby can be used modulate or alter the activity of the endothelin family of peptides. More particularly, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides and pharmaceutically acceptable derivatives of the peptides that specifically inhibit the activity of endothelin are provided. Among the cyclic peptides are those that have the formula: cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -D-Trp): X.sup.1 is D-Tyr or D-Asp; X.sup.2 is Phe, Ala, Ac.sub.3 c or Pro; X.sup.3 is D-His, D-Ala, D-Val, Gly or .beta.-Ala; and X.sup.4 is His, Ala, .beta.-Ala, Aib, Gly, D-His-gly or Leu; cyclo(X.sup.1 -L-Phe-X.sup.3 -X.sup.4 -X.sup.5) in which X.sup.1 is D-Tyr, D-Asp or D-Glu, X.sup.3 is selected from among D-His, .beta.-Ala-D-His or gly-D-His; X.sup.4 is Ser, Gly or .beta.-Ala, and X.sup.5 is D-Trp or N-Me-D-Trp; cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -L-Trp) in which X.sup.1 is D-Ala, Aib, Gly, D-Val, D-Leu, D-lle, D-Nva, D-Nle, or D-Alle; X.sup.2 is D-Val, D-Leu, D-lle, D-Ala, D-Gln, Gly, Aib, D-Nva, D-Nle, or D-Alle; X.sup.3 is Pro, Gly, Aib, Val, Leu, L-Nva, L-Nle, L-Alle or L-Hyp and X.sup.4 is D-Asp, D-Glu, D-Ser, D-Thr, D-Tyr, D-Cys(O.sub.3 H) or D-Pen(O.sub.3 H); and cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -L-Trp) in which X.sup.1 is D-Leu, D-Val, D-lle, D-Ala, Gly, Aib, D-Nva, D-Nle or D-Alle; X.sup.2 is Val, lle, Leu, Ala, Gln, Gly, Aib, L-Nva, L-Nle or L-Alle; X.sup.3 is D-Pro, D-Hyp, D-Ala, D-Val, D-lle, Gly, Aib, D-Nva, D-Nle or D-Alle; and X.sup.4 is Asp, Glu, Tyr, Ser, Thr, L-Cys(O.sub.3 H) or L-Pen(O.sub.3 H). Pharmaceutical compositions containing the peptides and methods of modulating the activity of endothelin peptides are also provided.